{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:33:58Z","timestamp":1790674438923,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T00:00:00Z","timestamp":1579651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005725","name":"CHDI Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Changes in phosphodiesterase 10A enzyme levels may be a suitable biomarker of disease progression in Huntington's disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To evaluate phosphodiesterase 10A PET imaging as a biomarker of HD progression using the radioligand, [<jats:sup>18<\/jats:sup>F]MNI\u2010659.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The cross\u2010sectional study (NCT02061722) included 45 Huntington's disease gene\u2010expansion carriers stratified into four disease stages (early and late premanifest and Huntington's disease stages 1 and 2) and 45 age\u2010 and sex\u2010matched healthy controls. The primary analysis compared striatal and pallidal phosphodiesterase 10A availability between Huntington's disease gene\u2010expansion carriers and healthy controls as assessed by [<jats:sup>18<\/jats:sup>F]MNI\u2010659 binding. We assessed changes in phosphodiesterase 10A expression using several PET methodologies and compared with previously proposed measures of Huntington's disease progression (PET imaging of D<jats:sub>2\/3<\/jats:sub> receptors and anatomical volume loss on MRI). The longitudinal follow\u2010up study (NCT02956148) continued evaluation of phosphodiesterase 10A availability in 35 Huntington's disease gene\u2010expansion carriers at a mean of 18 months from baseline of the cross\u2010sectional study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Primary analyses revealed that phosphodiesterase 10A availability in caudate, putamen, and globus pallidus was significantly lower in Huntington's disease gene\u2010expansion carriers versus healthy controls across all stages. Striatal and pallidal phosphodiesterase 10A availability progressively declined in the premanifest stages and appeared to plateau between stages 1 and 2. The percentage decline of phosphodiesterase 10A availability measured cross\u2010sectionally between Huntington's disease gene\u2010expansion carriers and healthy controls was greater than that demonstrated by D<jats:sub>2\/3<\/jats:sub> receptor availability or volumetric changes. Annualized rates of phosphodiesterase 10A change showed a statistically significant decline between the cross\u2010sectional study and follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>[<jats:sup>18<\/jats:sup>F]MNI\u2010659 PET imaging is a biologically plausible biomarker of Huntington's disease progression that is more sensitive than the dopamine\u2010receptor and volumetric methods currently used. \u00a9 2020 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.27963","type":"journal-article","created":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T07:02:56Z","timestamp":1579676576000},"page":"606-615","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["PET Molecular Imaging of Phosphodiesterase 10A: An Early Biomarker of Huntington's Disease Progression"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1863-1922","authenticated-orcid":false,"given":"Patrik","family":"Fazio","sequence":"first","affiliation":[{"name":"Centre for Psychiatry Research Department of Clinical Neuroscience, Karolinska Institutet, &amp; Stockholm Health Care Services  Region Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl J.","family":"Fitzer\u2010Attas","sequence":"additional","affiliation":[{"name":"CHDI Management\/CHDI Foundation  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ladislav","family":"Mrzljak","sequence":"additional","affiliation":[{"name":"CHDI Management\/CHDI Foundation  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Bronzova","sequence":"additional","affiliation":[{"name":"European Huntington's Disease Network University Hospital of Ulm  Ulm 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